ABSTRACT The overall goal of this proposal is to provide the training, career development, and mentorship that will result in the candidate Dr. Carroll?s ability to develop an independent program of research that brings genetic studies and personalized approaches to commercial smoking cessation treatment to the American Indian and Alaska Native (AI/AN) population. Dr. Carroll is an Assistant Professor at the University of Minnesota (UMN) School of Public Health with an appointment at the Masonic Cancer Center. Dr. Carroll completed graduate training in epidemiology and public health, and undergraduate training in molecular genetics. She completed a two year postdoctoral fellowship with the UMN Tobacco Research Programs with the support of an NIH T32 gaining expertise in clinical trials. During the five years of this career development award, Dr. Carroll plans to develop expertise in genetic contributors to smoking behavior, statistical analysis of genetic data, and qualitative data skills for understanding barriers to genetic research in AI/AN. These areas of new training are essential for the candidate to be able to fully serve Tribal communities who wish to embark upon genetic-based research and approaches to smoking cessation. The candidate has a strong mentorship team that includes world-renowned academic scientists and liaisons with the AI/AN community, and a relevant career development plan that will enable her to develop into a successful academic investigator and compete for independent funding through R01 grant mechanisms. The foundation of the research proposal is an existing collaboration with an AI Tribe with a commercial smoking prevalence >60%. The goal of Aim I is to examine nicotine metabolism genotype and phenotype data, which has evidence for optimizing cessation treatment, and relating to biomarkers of nicotine dose and smoking intensity, and nicotine dependence among AI smokers. The applicant will also explore social and cultural determinants of smoking behavior and therefore has the potential to provide a comprehensive picture for why AI smoke at such high rates and have poor quit success. Aim II utilizes focus groups to assess perceptions of and barriers to participating in genetic studies and genetically-informed approaches to cessation treatment and ways to overcome barriers among AI smokers and their healthcare providers. The goal of AIM III is to expand the candidate?s existing collaborations with AI Tribes so that the candidate can assist more Tribes in developing effective cessation interventions. Ultimately, the completion of this study will provide evidence of Dr. Carroll?s expertise in collaborating with AI tribes on a focused and highly feasible genetic study and will allow for her to pursue additional genetic studies and genetically-informed approaches to smoking cessation treatment in a population with a history of high smoking and low rates of participating in genetic research. The result of this proposal and investment in the Dr. Carroll?s continued training have the potential to dramatically reduce commercial cigarette smoking among the AI/AN population.